8. altered immunocompetence8. altered immunocompetence . updates . ... they are temperature...

General Best Practice Guidelines for Immunization: Altered Immunocompetence 119

8. Altered Immunocompetence

Updates

This section incorporates general content from the Infectious Diseases Society of

America policy statement, 2013 IDSA Clinical Practice Guideline for Vaccination of the

Immunocompromised Host (1), to which CDC provided input in November 2011. The

evidence supporting this guidance is based on expert opinion and arrived at by

consensus.

General Principles

Altered immunocompetence, a term often used synonymously with

immunosuppression, immunodeficiency, and immunocompromise, can be classified as

primary or secondary. Primary immunodeficiencies generally are inherited and include

conditions defined by an inherent absence or quantitative deficiency of cellular,

humoral, or both components that provide immunity. Examples include congenital

immunodeficiency diseases such as X-linked agammaglobulinemia, SCID, and chronic

granulomatous disease. Secondary immunodeficiency is acquired and is defined by loss

or qualitative deficiency in cellular or humoral immune components that occurs as a

result of a disease process or its therapy. Examples of secondary immunodeficiency

include HIV infection, hematopoietic malignancies, treatment with radiation, and

treatment with immunosuppressive drugs. The degree to which immunosuppressive

drugs cause clinically significant immunodeficiency generally is dose related and varies

by drug. Primary and secondary immunodeficiencies might include a combination of

deficits in both cellular and humoral immunity. Certain conditions like asplenia and

chronic renal disease also can cause altered immunocompetence.

Determination of altered immunocompetence is important to the vaccine provider

because incidence or severity of some vaccine-preventable diseases is higher in persons

with altered immunocompetence; therefore, certain vaccines (e.g., inactivated influenza

vaccine, pneumococcal vaccines) are recommended specifically for persons with these


diseases (2,3). Administration of live vaccines might need to be deferred until immune

function has improved. This is primarily a safety concern, because persons who have

altered immunocompetence and receive live vaccines might be at increased risk for an

adverse reaction because of uninhibited growth of the attenuated live virus or bacteria.

Vaccines might be less effective during the period of altered immunocompetence.

Inactivated vaccines might best be deferred during a period of altered

immunocompetence; in this circumstance, the concern is with effectiveness and not

safety. Additionally, if an inactivated vaccine is administered during the period of

altered immunocompetence, it might need to be repeated after immune function has

improved.

The degree of altered immunocompetence in a patient should be determined by a

physician. The challenge for clinicians and other health care providers is assessing the

safety and effectiveness of vaccines for conditions associated with primary or secondary

immunodeficiency, especially when new therapeutic modalities are being used and

information about the safety and effectiveness of vaccines has not been characterized

fully in persons receiving these drugs (Table 8-1). Laboratory studies can be useful for

assessing the effects of a disease or drug on the immune system. Tests useful to assess

humoral immunity include immunoglobulin (and immunoglobulin subset) levels and

specific antibody levels (e.g., tetanus and diphtheria). Tests that demonstrate the status

of cellular immunity include lymphocyte numbers (i.e., a complete blood count with

differential), a test that delineates concentrations and proportions of lymphocyte

subsets (i.e., B and T lymphocytes, CD4+ B lymphocytes versus CD8+ T lymphocytes),

and tests that measure T-cell proliferation or function in response to specific or

nonspecific stimuli (e.g., lymphocyte proliferation assays) (4,5). The ability to

characterize a drug or disease condition as affecting cellular or humoral immunity is

only the first step; using this information to draw inferences about whether particular

vaccines are indicated or whether caution is advised with use of live or inactivated

vaccines is more complicated and might require consultation with an infectious diseases

or immunology specialist.


Altered Immunocompetence as an Indication to Receive a

Vaccine Outside of Routinely Recommended Age Groups

This section describes situations in which vaccines are recommended outside of the

routine-age-based recommendation because the risk for vaccine-preventable disease is

increased due to altered immunocompetence. Persons with altered immunocompetence

generally are recommended to receive polysaccharide-based vaccines (PCV13, PPSV23,

and Hib), on the basis of increased risk for disease if the vaccine is withheld. For certain

specific categories of altered immunocompetence, patients are also recommended to

receive polysaccharide based vaccines (MenACWY, Hib-MenCY, and MPSV4).

Pneumococcal Vaccines

Two types of vaccine against invasive pneumococcal disease are available in the United

States: PCV13 and PPSV23. PCV13 is recommended routinely for all children beginning

at age 2 months through age 59 months and for adults aged 65 years or older. PCV13 is

also recommended for children, adolescents, and adults with conditions that place them

at high risk for invasive disease from Streptococcus pneumoniae. PCV13 is

recommended for persons aged 6-64 years who have not previously received PCV13 and

have congenital immunodeficiency disorders (including B- or T-lymphocyte deficiency,

complement deficiencies, and phagocytic disorders), anatomic or functional asplenia

(including sickle cell disease and other hemoglobinopathies), HIV infection, cochlear

implant, cerebrospinal fluid leak, chronic renal failure, nephrotic syndrome, iatrogenic

immunosuppression, or other immunocompromising conditions.

PPSV23 is licensed for use in persons aged ≥2 years and recommended routinely for

adults aged 65 years and older. PPSV23 is also recommended for persons age 2 through

64 years with congenital immunodeficiency disorders, anatomical and functional

asplenia, HIV infection, cochlear implant, cerebrospinal fluid leak, and iatrogenic

immunosuppression. Complete recommendations on use of PCV13 and PPSV23 are

available in the Recommended Immunization Schedules for Persons Aged 0 Through 18

Years and the Recommended Adult Immunization Schedule (2,6).


Meningococcal Vaccines

Three types of meningococcal vaccines are licensed in the United States: meningococcal

conjugate (MenACWY and Hib-MenCY), meningococcal polysaccharide (MPSV4), and

serogroup B meningococcal (MenB) vaccines. Persons with functional or anatomic

asplenia (including sickle cell disease) and persistent complement component deficiency

(including persons taking eculizumab [Soliris]) (7) are at increased risk for

meningococcal disease and should receive both MenACWY and MenB vaccines. For

children 2 months through 23 months of age, an age-appropriate series of

meningococcal conjugate vaccine should be administered. If MenACWY-D (Menactra) is

administered to a child with asplenia, it should be after 2 years of age and at least 4

weeks after the completion of all PCV13 doses. A 2-dose primary series of either

MenACWY-CRM (Menveo) or MenACWY-D (Menactra) should be administered to

persons 2 years of age or older with asplenia or complement deficiency. Following the

primary series of vaccine, a 3-year interval to the next dose is recommended for persons

who received their previous dose at younger than 7 years. A 5-year interval is

recommended for persons who received their previous dose at age 7 years or older.

Although MPSV4 is the only meningococcal vaccine licensed for persons older than 55

years of age, adults 56 years and older with asplenia or complement deficiency should be

vaccinated with MenACWY-CRM or MenACWY-D rather than MPSV4 (8).

Meningococcal serogroup B vaccines are licensed for persons 10-25 years of age and are

recommended for persons 10 years of age or older for persons with high-risk conditions

like functional or anatomic asplenia or persistent complement component deficiency.

There are presently no recommendations for booster doses of either MenB vaccine

(9,10). Complete recommendations for use of meningococcal vaccines are available in

the Recommended Immunization Schedules for Persons Aged 0 Through 18 Years and

the Recommended Adult Schedule (2,6).


Hib Vaccines

Hib conjugate vaccines are available in single or combined antigen preparations. Hib ––

vaccine is recommended routinely for all children through age 59 months. Children 12

through 59 months who are at high risk for invasive Hib disease (i.e., recipients of

chemotherapy or radiation for malignant neoplasms, or those with functional or

anatomic asplenia, HIV infection, immunoglobulin deficiency, or early complement

component deficiency) and who are unvaccinated or received only one dose of Hib

vaccine before 12 months of age should receive 2 additional doses of Hib vaccine; those

who received 2 or more doses of Hib before 12 months of age should receive one

additional dose. A child younger than 5 years of age receiving chemotherapy or

radiation therapy should have Hib doses repeated if the doses were received during

therapy or within 14 days of starting therapy; repeat doses should be started at least 3

months after completion of therapy. Recipients of hematopoietic cell transplants should

be revaccinated with 3 doses of Hib vaccine, starting 6-12 months after successful

transplant, regardless of vaccination history or age. Children 5-18 years of age with HIV

who are unimmunized(a) should receive a dose of Hib vaccine; Hib vaccination is not

recommended in HIV-infected adults. Unimmunized(a) asplenic patients older than 59

months of age or adults should receive a dose of Hib vaccine. Anyone 15 months of age

or older who is undergoing a splenectomy and is unimmunized(a) should receive a dose

of Hib vaccine (11). Complete recommendations for use of Hib vaccine are available in

the Recommended Immunization Schedules for Persons Aged 0 Through 18 Years and

the Recommended Adult Immunization Schedule (2,6).


Vaccination of Contacts of Persons with Altered

Immunocompetence

Household contacts and other close contacts of persons with altered

immunocompetence should receive all age- and exposure-appropriate vaccines, with the

exception of smallpox vaccine (12,13). Receipt of vaccines will prevent the vaccine-

preventable disease, so there can be no potential transmission to the contact with

altered immunocompetence. The live MMR, varicella, and rotavirus vaccines should be

administered to susceptible household contacts and other close contacts of

immunocompromised patients when indicated. Zoster vaccine can be administered

when indicated. MMR vaccine viruses are not transmitted to contacts, and transmission

of varicella-zoster virus vaccine strain is rare (14,15). No specific precautions are needed

unless the varicella vaccine recipient has a rash after vaccination, in which case direct

contact with susceptible household contacts with altered immunocompetence should be

avoided until the rash resolves (14,15). All members of the household should wash their

hands after changing the diaper of an infant who received rotavirus vaccine. This

minimizes rotavirus transmission, as shedding may occur up to one month after the last

dose (16,17). Household and other close contacts of persons with altered

immunocompetence should receive annual influenza vaccination. Introduction of low

levels of vaccine viruses into the environment likely is unavoidable when administering

LAIV. LAIV vaccine viruses are cold-adapted, so they can replicate in the nose and

generate an immune response without entering the lungs (i.e., they are temperature

sensitive and replicate poorly at core body temperatures). No instances have been

reported of illness caused by attenuated vaccine virus infections among health care

providers or immunocompromised patients. LAIV may be administered to healthy

household and other close contacts of persons with altered immunocompetence unless

the person with altered immunocompetence is in a protective environment, typically

defined as a specialized patient-care area with a positive airflow relative to the corridor,

high-efficiency particulate air filtration, and frequent air changes (3). No preference

exists for inactivated influenza vaccine use by health care workers or other persons who

have close contact with persons with lesser degrees of immunosuppression (e.g.,


persons with diabetes, persons with asthma taking high-dose corticosteroids, or persons

infected with HIV), and no preference exists for inactivated influenza vaccine use by

health care workers or other healthy persons aged 5-49 years in close contact with all

other groups at high risk.

Inactivated Vaccines: Safety

All inactivated vaccines can be administered safely to persons with altered

immunocompetence, whether the vaccine is a killed whole-organism or a recombinant,

subunit, split-virus, toxoid, polysaccharide, or polysaccharide protein-conjugate vaccine.

Inactivated Vaccines: Effectiveness

Except for inactivated influenza vaccine, vaccination during chemotherapy or radiation

therapy should be avoided if possible because antibody response might be suboptimal.

Patients vaccinated within a 14-day period before starting immunosuppressive therapy

or while receiving immunosuppressive therapy should be considered unimmunized and

should be revaccinated at least 3 months after therapy is discontinued if immune

competence has been restored. Patients who have quantitative B-cell deficiencies and

are receiving immunoglobulin therapy should not receive either inactivated or live

vaccines while receiving the immunoglobulin therapy because of concerns about

effectiveness of the vaccines. Patients on chemotherapy with anti-B cell antibodies (e.g.,

rituximab) should wait at least 6 months after therapy before being vaccinated with

inactivated vaccines. Some experts recommended longer than 6 months for some anti-B

cell antibodies. For other forms of altered immunocompetence, if inactivated vaccines

are indicated, the usual schedules are recommended. However, the effectiveness of such

vaccinations might be suboptimal (1).


Live, Attenuated Viral and Bacterial Vaccines: Effectiveness

The same rationale regarding effectiveness that exists with inactivated vaccines also

exists with live vaccines.

Live, Attenuated Viral and Bacterial Vaccines: Safety

Severe complications have followed vaccination with certain live, attenuated viral and

live, attenuated bacterial vaccines among persons with altered immunocompetence (18-

26). Persons with most forms of altered immunocompetence should not receive live

vaccines (MMR, varicella, MMRV, LAIV, zoster, yellow fever, Ty21a oral typhoid, BCG,

smallpox, and rotavirus). However, exceptions exist, and are discussed in this section.

Patients with any defect in phagocytic function (e.g., chronic granulomatous disease,

leukocyte adhesion deficiency, myeloperoxidase deficiency, Chediak-Higashi syndrome)

should NOT receive live bacterial vaccines. Patients with a specific type of defect in

phagocytic function—chronic granulomatous disease—should receive otherwise

indicated live attenuated viral vaccines in addition to inactivated vaccines but should

NOT receive live bacterial vaccines. Patients with defects in phagocytic function that are

undefined or known to be accompanied by defects in T-cell and natural killer cell

function (e.g., leukocyte adhesion deficiency, myeloperoxidase deficiency, Chediak-

Higashi syndrome) should NOT receive live attenuated viral or bacterial vaccines. These

conditions include specific deficits in T-cell and natural killer cell function, reducing the

response to live viral vaccine antigens to an extent not seen in chronic granulomatous

disease (1). Children with deficiencies in complement should receive otherwise indicated

live, attenuated viral and live, attenuated bacterial vaccines. Children with asplenia

should not receive LAIV, but can receive other indicated live, attenuated viral and live,

attenuated bacterial vaccines.


Persons with severe cell-mediated immunodeficiency should not receive live, attenuated

viral or bacterial vaccines. Patients with defects of the interferon-gamma/interleukin-12

axis should not receive live bacterial vaccines. Patients with deficiencies of interferon-

gamma or interferon-alpha should not receive live viral or live bacterial vaccine. These

defects involve a deficiency in cytokine production which affects the immune response

to a wide scope of antigens, both bacterial and viral (1). Two factors support vaccination

of HIV-exposed or HIV-infected infants with rotavirus vaccines: 1) the HIV diagnosis

might not be established in infants born to HIV-infected mothers before the age of the

first rotavirus vaccine dose (only 1.5%-3% of HIV-exposed infants in the United States

will be determined to be HIV-infected), and 2) the vaccine strains of rotavirus are

considerably attenuated. Patients taking exogenous interferon as therapy should not

receive live bacterial or live viral vaccines.

Children with HIV infection are at increased risk for complications from varicella and

herpes zoster infection compared with immunocompetent children (27,28). Limited

data among HIV-infected children younger than 8 years (specifically, those individuals

with CDC class N, A, or B with age-specific CD4+ T-lymphocyte percentages of ≥15%)

indicate that single-component varicella vaccine is immunogenic, effective, and safe

(14,28). Data on use of varicella vaccine in HIV-infected adolescents and adults are

lacking. However, on the basis of expert opinion, the safety of varicella vaccine in HIV-

infected persons older than 8 years with comparable levels of immune function

(CD4+T-lymphocyte count greater than 200 cells/mm3) is likely to be similar to that of

children aged younger than 8 years (14). Varicella vaccine should be considered for

persons who meet these criteria. Eligible HIV-infected persons 12 months of age or

older should receive 2 doses of single-component varicella vaccine with a 3-month

interval between doses (14,28). Doses separated by <3 months are invalid for persons

with HIV infection. MMRV vaccine should not be administered to any HIV-infected

person.

Persons with HIV infection are at increased risk for severe complications if infected with

measles. No severe or unusual adverse events have been reported after measles

vaccination among HIV-infected persons who did not have evidence of severe


immunosuppression (29-32). Two doses of MMR vaccine are recommended for all HIV-

infected individuals aged ≥12 months who do not have evidence of current severe

immunosuppression (i.e., individuals aged ≤5 years must have CD4+T lymphocyte

[CD4+] percentages ≥15% for ≥6 months, and individuals aged >5 years must have

CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) and do not

have current evidence of measles, rubella, and mumps immunity. In cases when only

CD4+cell counts or only CD4+percentages are available for those >5 years, the

assessment of severe immunosuppression can be based on the CD4+values (count or

percentage) that are available. In cases when CD4+percentages are not available for

those aged ≤5 years, the assessment of severe immunosuppression can be based on age-

specific CD4+counts at the time CD4+counts were measured; i.e., absence of severe

immunosuppression is defined as ≥6 months above age-specific CD4+count criteria:

CD4+count >750 lymphocytes/mm3 while aged ≤12 months and CD4+count ≥500

lymphocytes/mm3 while aged 1 through 5 years (33). Similarly, repeat doses of MMR

vaccination are recommended for individuals with perinatal HIV infection who were

vaccinated prior to establishment of effective combination antiretroviral therapy

(cART). They should receive 2 appropriately spaced doses of MMR vaccine once

effective cART has been established (individuals aged ≤5 years must have

CD4+percentages ≥15% for ≥6 months; individuals aged >5 years must have

CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) unless they

have other acceptable current evidence of measles, rubella, and mumps immunity.

HIV-infected persons who are receiving regular doses of IGIV are unlikely to respond to

varicella vaccine or MMR vaccine because of the continued presence of passively

acquired antibody. However, because of the potential benefit, MMR and varicella

vaccines should be considered approximately 14 days before the next scheduled dose of

IGIV (if not otherwise contraindicated), although an optimal immune response might

not occur depending on the presence of neutralizing antibodies against the vaccine

virus. Vaccination should be repeated (if not otherwise contraindicated) after the

recommended interval (see Table 3-5 in the Timing and Spacing of Immunobiologics of

this document). In most cases, this is after the therapy has been discontinued.


Patients with leukemia, lymphoma, or other malignancies whose disease is in remission,

who have restored immunocompetence, and whose chemotherapy has been

discontinued for at least 3 months can receive live-virus vaccines. Persons with impaired

humoral immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) may be

vaccinated with varicella vaccine (14). However, most persons with these disorders also

receive periodic doses of IGIV. Appropriate spacing should be maintained between

administration of IGIV and varicella vaccine in an attempt to prevent an inadequate

response to vaccination caused by the presence of neutralizing antibodies from the IGIV.

Zoster incidence is higher in persons with altered immunocompetence (34). Adults with

most types of altered immunocompetence are expected to maintain residual immunity

to varicella-zoster virus because of chronic latent infection that protects against primary

varicella but provides incomplete protection against zoster. Zoster vaccine is

contraindicated in persons with primary or acquired immunodeficiency (e.g.,

lymphoma, leukemia, tumors involving bone marrow, and patients receiving

chemotherapy) and some HIV infected patients (34). Zoster vaccine may be

administered to certain persons age 60 or older with altered immunocompetence, such

as persons receiving low dosages of immunosuppressive medications, those with

isolated B-cell deficiencies (i.e., impaired humoral immunity), or those with HIV

infection who have CD4+ T-lymphocyte counts >200 cells/mm3.

Recipients of Hematopoietic Cell Transplants

A hematopoietic cell transplant (HCT) results in immunosuppression because of the

hematopoietic ablative therapy administered before the transplant, drugs used to

prevent or treat graft-versus-host disease, and, in some cases, from the underlying

disease process necessitating transplantation (35-37). HCT involves ablation of the bone

marrow followed by reimplantation of the person’s own stem cells or stem cells from a

donor. Antibody titers to vaccine-preventable diseases (e.g., tetanus, poliovirus,

measles, mumps, rubella, and encapsulated bacteria) decrease 1-4 years after autologous

or allogeneic HCT if the recipient is not revaccinated. HCT recipients of all ages are at

increased risk for certain vaccine-preventable diseases, including diseases caused by


encapsulated bacteria (i.e., pneumococcal, meningococcal, and Hib infections). As a

result, HCT recipients who received vaccines prior to their HCT should be revaccinated

routinely after HCT, regardless of the source of the transplanted stem cells (35-37).

Vaccination or revaccination doses of pneumococcal vaccines, DTaP vaccine, Hib

vaccine, hepatitis A vaccine, hepatitis B vaccine, meningococcal vaccines, IPV,

inactivated influenza vaccines, and human papillomavirus (HPV) vaccines (for

individuals aged 9-26 years) are recommended after HCT (1,35). Varicella, zoster, and

MMR vaccines may be administered after HCT if 24 months have passed since HCT, the

patient does NOT have graft-vs-host disease, and is considered immunocompetent.

Yellow fever vaccine, rabies vaccine, tick-borne encephalitis vaccine, and Japanese

encephalitis vaccine are not routinely administered vaccines, so their use post-HCT will

be driven by a disease-specific risk such as exposure or travel. If someone has received

yellow fever vaccine prior to an HCT, another dose should be administered post-HCT

(38). BCG, LAIV, typhoid vaccine, and rotavirus vaccine are not recommended after

HCT. Most inactivated vaccines should be initiated 6 months after the HCT (37).

Inactivated influenza vaccine should be administered beginning at least 6 months after

HCT and annually thereafter for the life of the patient. A dose of inactivated influenza

vaccine can be given as early as 4 months after HCT, but a second dose should be

considered in this situation (37). A second dose is recommended routinely for all

children younger than 9 years receiving influenza vaccine for the first time. Sequential

administration of 3 doses of pneumococcal conjugate vaccine is recommended,

beginning 3-6 months after the transplant, followed by a dose of PPSV23 (35). Some

sources state a 4-week interval between these doses as reasonable with the dose of

PPSV23 being replaced by a dose of PCV13 in the context of graft-versus-host disease

(35). Others sources support 3 doses of PCV13 at 8-week intervals, with a dose of

PPSV23 recommended 8 weeks after the last dose of PCV13 and 12 months after the

HCT (1). A 3-dose regimen of Hib vaccine should be administered beginning 6 months

after transplant; at least 1 month should separate the doses (37). This series should be

given regardless of whether or not vaccine doses were administered prior to the HCT.

The revaccination schedule for pertussis-containing vaccines includes 3 doses of DTaP

for patients <7 years (14). For patients ≥7 years, providers have 3 options for


revaccination: 1) 3 doses of DTaP; 2) one dose of Tdap and 2 doses of DT; or 3) one dose

of Tdap and 2 doses of Td (1).

Providers need to make a clinical judgment whether they will follow the revaccination

schedule described above, even if doses were not administered prior to the HCT. There

are specific recommendations for Hib and pertussis-containing vaccines. Use of the 3-

dose Hib schedule following HCT is supported for both patients that received Hib prior

to HCT and those who did not receive Hib prior to HCT (6,11). For children >6 years

who did not receive previous doses of pertussis-containing vaccine prior to the HCT, the

preferred schedule following HCT is a dose of Tdap followed by 2 doses of Td (personal

communication, subject matter experts). This is identical to one of the alternative

regimens for revaccination doses, described above.

Conditions or Drugs that Might Cause Immunodeficiencies

Asplenia and use of corticosteroids or certain drugs have the potential to be

immunosuppressive and are presumed to cause some degree of altered

immunocompetence.

Anatomic or Functional Asplenia

Persons with anatomic asplenia (e.g., surgical removal or congenital absence of the

spleen) or functional asplenia (as occurs in persons with sickle cell disease) are at

increased risk for infection by encapsulated bacteria, especially S. pneumoniae

(pneumococcus), N. meningitidis (meningococcus), and Hib (7,8,39). Children should

receive an age-appropriate series of PCV13. Unvaccinated children 2-5 years should

receive 2 doses of PCV13. Children ≥6 years should receive a dose of PCV13 if they have

not previously received a dose of PCV13. Persons aged ≥2 years should receive 2 doses of

PPSV23 separated by 5 years, beginning 8 or more weeks after completing all

recommended doses of PCV13 (6,7,40,41). In circumstances where both PCV13 and

PPSV23 are indicated, doses of PCV13 should be administered first followed by PPSV23

8 weeks after the last dose of PCV13.


Meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines are

recommended for persons with anatomic or functional asplenia (including sickle cell

disease). For children 2-23 months of age, a series of MenACWY-CRM (Menveo) or Hib-

MenCY (MenHibrix) should be administered. For persons ≥2 years of age, a 2-dose

primary series of either MenACWY-CRM or MenACWY-D (Menactra) should be

administered. If a person with functional or anatomic asplenia is catching up on

pneumococcal conjugate vaccine (PCV13), and the provider only carries MenACWY-D,

indicated doses of PCV13 should be completed first and MenACWY-D should be given 4

weeks after the PCV13 series is completed. Following the primary series of vaccine, a 3-

year interval to the next dose is recommended for asplenic children who received their

last previous dose at age younger than 7 years. A 5-year interval for asplenic persons is

recommended for persons who received their last previous dose at age 7 years or older.

Meningococcal B (MenB) vaccine should be administered as either a 2-dose series of

MenB-4C (Bexsero) or a 3-dose series of MenB-FHbp (Trumenba). The same vaccine

product must be used for all doses. Based on available data and expert opinion, MenB-

4C or MenB-FHbp may be administered concomitantly with MenACWY vaccines, but at

a different anatomic site, if feasible. There are presently no recommendations for

booster doses of either MenB vaccine.

Hib vaccine is recommended routinely for all children through age 59 months. Children

12-59 months with functional or anatomic asplenia and who are unvaccinated or who

received only one dose of Hib disease before 12 months of age should receive 2 doses of

Hib vaccine; those who received 2 or more doses of Hib before 12 months of age should

receive one additional dose. Unimmunized(a) asplenic patients older than 59 months of

age should receive one dose of Hib vaccine. Anyone ≥15 months of age who is

undergoing a splenectomy and is unimmunized(a) should receive one dose of Hib

vaccine.

Pneumococcal, meningococcal, and Hib vaccinations should be administered at least 14

days before elective splenectomy, if possible. If the vaccinations are not administered

before surgery, they should be administered after the procedure as soon as the patient’s

condition is stable.


Corticosteroids

The amount of systemically absorbed corticosteroids and the duration of administration

needed to suppress the immune system of an otherwise immunocompetent person are

not well defined. Although the immunosuppressive effects of steroid treatment vary, the

majority of clinicians consider a dose equivalent to either ≥2 mg/kg of body weight or

≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg when

administered for ≥14 consecutive days as sufficiently immunosuppressive to raise

concern about the safety of vaccination with live-virus vaccines (37). This dosage is

referred to as “high-dose corticosteroids”. Corticosteroids used in greater than

physiologic doses also can reduce the immune response to vaccines. Vaccination

providers should defer live-virus vaccination for at least 1 month after discontinuation

of high-dose systemically absorbed corticosteroid therapy administered for ≥14 days.

Following vaccination, the decision needs to be made when to restart

immunosuppressive therapy. There are no specific recommendations about when to

restart immunosuppressive medicines. However, when initiating immunosuppressive

therapy, providers should wait 4 weeks after a live vaccine and 2 weeks after an

inactivated vaccine. However, if patients require therapy for chronic inflammatory

conditions, this therapy should not be delayed because of past administration of

vaccines (1).

Corticosteroid therapy usually is not a contraindication to administering live-virus

vaccine when administration is 1) short term (i.e., <14 days); 2) a low to moderate dose

(i.e., <20 mg of prednisone or equivalent per day or <2mg/kg body weight per day for a

young child); 3) long-term, alternate-day treatment with short-acting preparations; 4)

maintenance physiologic doses (replacement therapy); or 5) topical (skin or eyes),

inhaled, or by intra-articular, bursal, or tendon injection (37). No evidence of an

increased risk for more severe reactions to live, attenuated viral vaccines has been

reported among persons receiving corticosteroid therapy by aerosol, and such therapy is

not a reason to delay vaccination.


Other Immunosuppressive Drugs

When feasible, clinicians should administer all indicated vaccines before initiation of

chemotherapy, before treatment with other immunosuppressive drugs, and before

radiation or splenectomy. Persons receiving chemotherapy or radiation for leukemia

and other hematopoietic malignancies, or for solid tumors, should be assumed to have

altered immunocompetence. Live, attenuated vaccines should not be administered for at

least 3 months after such immunosuppressive therapy. Inactivated vaccines

administered during chemotherapy should be readministered after immune competence

is regained. Children vaccinated before receiving chemotherapy for leukemia,

lymphoma, other malignancies, or radiation generally are thought to retain immune

memory after treatment, although revaccination with the common childhood vaccines

after chemotherapy for acute lymphoblastic leukemia might be indicated (42). In

general, revaccination of a person after chemotherapy or radiation therapy is considered

unnecessary if the previous vaccination occurred before therapy and not during therapy,

with the exception of recipients of HCT, who should be revaccinated as recommended

previously. Determination of the level of immune memory and the need for

revaccination should be made by the treating physician.

Certain immunosuppressive medications are administered to prevent solid organ

transplant rejection. Live vaccines should be withheld for 2 months following

discontinuation of anti-rejection therapies in patients with a solid organ transplant.

Zoster vaccine should be withheld one month following discontinuation of anti-rejection

therapies (34).

Other immunosuppressive medications include human immune mediators like

interleukins and colony-stimulating factors, immune modulators, and medicines like

tumor necrosis factor-alpha inhibitors and anti-B cell antibodies. Inactivated and live

vaccines should be administered 2 or more weeks before initiating such therapies. Live

vaccines should be withheld 3 months following such therapies, and both inactivated

and live vaccines should be withheld at least 6 months following therapy with anti-B cell

antibodies. Some experts recommend longer than 6 months following anti-B cell


antibodies. Anti-B cell antibodies suppress antibody-producing cells for a prolonged

duration, hence the longer interval recommended before administering vaccines (17).

Zoster vaccine is an exception and should be withheld 1 month following anti-B cell

antibodies.

(a) Patients who have not received a primary series and booster dose or at least 1 dose of Hib vaccine after 14 months of age are

considered unimmunized.


TABLE 8-1. Vaccination of persons with primary and secondary immunodeficiencies Primary Specific

immunodeficiency

Contraindicated vaccines(a)

Risk-specific recommended vaccines(a)

Effectiveness and comments

B-lymphocyte (humoral)

Severe antibody deficiencies (e.g., X-linked agammaglobulinemia and common variable immunodeficiency)

OPV(b) Smallpox(c) LAIV BCG Ty21a (live typhoid) Yellow fever MMR MMRV

Pneumococcal Hib (children 12-59 months of age)(d)

The effectiveness of any vaccine is uncertain if it depends only on the humoral response (e.g., PPSV23or MPSV4) IGIV interferes with the immune response to measles vaccine and possibly varicella vaccine

Less severe antibody deficiencies (e.g., selective IgA deficiency and IgG subclass deficiency)

OPV(b) BCG Yellow fever(e) Other live vaccines appear to be safe


All vaccines likely effective; immune response might be attenuated

T-lymphocyte (cell-mediated and humoral)

Complete defects (e.g., SCID disease, complete DiGeorge syndrome)

All live vaccines(f),(g),(h)


Vaccines likely to be effective


Partial defects (e.g., most patients with DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia- telangiectasia)

All live vaccines(f),(g),(h)

Pneumococcal Meningococcal Hib (children 12-59 months of age)(d)

Effectiveness of any vaccine depends on degree of immune suppression

Interferon-gamma/ Interleukin 12 axis deficiencies

All live bacterial vaccines (All live vaccines contraindicated in Interferon-gamma or interferon-alpha deficiencies)

None

Complement

Persistent complement, properdin, or factor B deficiency;

None Pneumococcal Meningococcal Hib (children 12-59 months of age)(d)

All routine vaccines likely effective

Taking eculizumab (Soliris)

None Meningococcal

Phagocytic function

Chronic granulomatous disease

Live bacterial vaccines(f)

None Live viral vaccines likely safe and effective


Phagocytic deficiencies that are undefined or accompanied by defects in T-cell and NK cell dysfunction (such as a Chediak-Higashi syndrome, Leukocyte Adhesion Deficiency [LAD], and myeloperoxidase deficiency)

MMR MMRV Varicella OPV(b) Smallpox BCG LAIV Ty21a Yellow Fever and bacterial vaccines(f),(g)

Pneumococcal All inactivated vaccines safe and likely effective

Secondary HIV/AIDS OPV(b) Smallpox BCG LAIV MMRV Withhold MMR, varicella, and zoster in severely immunocompromised persons Yellow fever vaccine might have a contraindication or a precaution depending on clinical parameters of immune function(i)

Pneumococcal Hib(d), (j) HepB

MMR and Varicella vaccine in those with mild immunosuppression, rotavirus, and all inactivated vaccines, including inactivated influenza as per routine vaccination schedule, might be effective(k)

Generalized malignant neoplasm, transplantation, immunosuppres

Live viral and bacterial, depending on immune status(f),(g),(l)

Pneumococcal Hib(m)

Effectiveness of any vaccine depends on degree of


sive or radiation therapy

immune suppression

Asplenia LAIV Pneumococcal Meningococcal Hib(d),(n)


Chronic renal disease

LAIV Pneumococcal HepB(o)


Abbreviations: AIDS = acquired immunodeficiency syndrome; BCG = bacille Calmette-Guérin; HepB = hepatitis B; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; IG = immunoglobulin; IGIV = immune globulin intravenous; IgA = immune globulin A; IgG = immune globulin G; LAIV = live, attenuated influenza vaccine; MMR = measles, mumps, and rubella; MMRV = measles, mumps, rubella, and varicella; MPSV4 = quadrivalent meningococcal polysaccharide vaccine; OPV = oral poliovirus vaccine (live); PPSV23= pneumococcal polysaccharide vaccine; SCID = severe combined immunodeficiency; Ty21a = live oral typhoid vaccine.

Source: (43). (a) Other vaccines that are universally or routinely recommended should be given if not contraindicated. An exception is patients with B-cell deficiencies receiving immunoglobulins, who should not receive either live or inactivated vaccines, due to safety (live vaccines) and efficacy (live and inactivated vaccines) concerns. (b) OPV is no longer available in the United States. (c) This table refers to contraindications for nonemergency vaccination (i.e., the ACIP recommendations); emergency response recommendations are addressed in the clinical guidance for smallpox vaccine use in an emergency. (d) Children 12-59 months: if unimmunized or received zero or only 1 dose, and that dose was administered before 12 months of age, should receive 2 Hib doses, 8 weeks apart; if received 2 or more doses before age 12 months, and none after 12 months, should receive 1 Hib dose 8 weeks after the last dose; if completed a primary series and received a booster dose at age 12 months or older, no additional Hib doses are recommended. (e) There are no data to support IgA deficiency as a contraindication for yellow fever vaccine. (f) Live bacterial vaccines: BCG, adenovirus, and oral Ty21a Salmonella Typhi vaccine. (g) Live viral vaccines: MMR, MMRV, OPV, LAIV, yellow fever, zoster, rotavirus, varicella, and vaccinia (smallpox). Nonemergency smallpox vaccination is not recommended for children younger than 18 years or the general public. (h) Regarding T-lymphocyte immunodeficiency as a contraindication for rotavirus vaccine, data exist only for SCID. (i) Symptomatic HIV infection or CD4+ T-lymphocyte count of <200/mm3 or <15% of total lymphocytes for children aged <6 years is a contraindication to yellow fever vaccine administration. Asymptomatic HIV infection with CD4+ T-lymphocyte count of 200-499/mm3 for persons aged ≥6 years or 15%-24% of total lymphocytes for children aged <6 years is a precaution for yellow fever vaccine administration. Details of yellow fever vaccine recommendations are available from CDC (44) (j) Patients 5-18 years of age who have not received a Hib primary series and a booster dose or at least one Hib dose after 14 months of age. (k) HIV-infected children should be considered for varicella vaccine if CD4+ T-lymphocyte count is ≥15% and should receive MMR vaccine if they are aged ≥12 months and do not have 1) evidence of current severe immunosuppression (i.e., individuals aged ≤5 years must have CD4+T lymphocyte [CD4] percentages ≥15% for ≥6 months; and individuals aged >5 years must have CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) and 2) other current evidence of measles, rubella, and mumps immunity. In cases when only CD4+cell counts or only CD4+percentages are available for those older than age 5 years, the assessment of severe


immunosuppression can be based on the CD4+values (count or percentage) that are available. In cases when CD4+percentages are not available for those aged ≤5 years, the assessment of severe immunosuppression can be based on age-specific CD4+counts at the time CD4+counts were measured; i.e., absence of severe immunosuppression is defined as ≥6 months above age-specific CD4+count criteria: CD4+count >750 lymphocytes/mm3 while aged ≤12 months and CD4+count ≥500 lymphocytes/mm3 while aged 1 through 5 years (33). (l) Withholding inactivated vaccines also is recommended with some forms of immunosuppressive therapy, like anti-CD20 antibodies, induction or consolidation chemotherapy, or patients with major antibody deficiencies receiving immunoglobulins. Inactivated influenza vaccine is an exception, but consideration should be given to repeating doses of any inactivated vaccine administered during these therapies. (m) Persons younger than 60 months undergoing chemotherapy or radiation therapy who have not received a Hib primary series and a booster dose or at least one Hib dose after 14 months of age; HCT patients of any ages, regardless of Hib vaccine history. (n) Persons older than 59 months who are asplenic and persons 15 months or older who are undergoing elective splenectomy who have not received a Hib primary series and a booster dose or at least one Hib dose after 14 months of age.

(o) Indicated based on the risk from dialysis-based bloodborne transmission.


REFERENCES 1. Rubin L, Levin M, Ljungman P, et al. 2013 IDSA clinical practice guideline for

vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-

100. DOI: 10.1093/cid/cit684

2. Kim DK, Bridges CB, Harriman KH. Advisory committee on immunization

practices recommended immunization schedule for adults aged 19 years or

older—United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):91-92.

3. Grohskopf LA, Olsen SJ, Sokolow LZ, et al. Prevention and control of seasonal

influenza with vaccines: recommendations of the Advisory Committee on

Immunization Practices (ACIP)—United States, 2014-15 influenza season.

MMWR Morb Mortal Wkly Rep. 2014;63(32):691-697.

4. Markert ML, Hummell DS, Rosenblatt HM, et al. Complete DiGeorge syndrome:

persistence of profound immunodeficiency. J Pediatr. 1998;132(1):15-21. DOI:

10.1016/S0022-3476(98)70478-0

5. Jeffrey Modell Foundation Medical Advisory Board. 10 warning signs of primary

immunodeficiency [Poster]. 2009; http:// www.info4pi.org/library/educational-

materials/10-warning-signs. Accessed 9 March, 2017.

6. Strikas RA. Advisory committee on immunization practices recommended

immunization schedules for persons aged 0 through 18 years—United States,

2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):93-94.

7. Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease.

Recommendations of the Advisory Committee on Immunization Practices

(ACIP). MMWR Recomm Rep. 2005;54(RR-7):1-21.

8. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal

disease: recommendations of the Advisory Committee on Immunization Practices


9. Folaranmi T, Rubin L, Martin SW, Patel M, MacNeil JR. Use of serogroup B

meningococcal vaccines in persons aged >/=10 years at increased risk for

serogroup B meningococcal disease: recommendations of the Advisory

Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep.

2015;64(22):608-612.


10. MacNeil JR, Rubin L, Folaranmi T, Ortega-Sanchez IR, Patel M, Martin SW. Use

of serogroup B meningococcal vaccines in adolescents and young adults:

recommendations of the Advisory Committee on Immunization Practices, 2015.

MMWR Morb Mortal Wkly Rep. 2015;64(41):1171-1176. DOI:

10.15585/mmwr.mm6441a3

11. Briere EC, Rubin L, Moro PL, Cohn A, Clark T, Messonnier N. Prevention and

control of Haemophilus influenzae type b disease: recommendations of the

advisory committee on immunization practices (ACIP). MMWR Recomm Rep.

2014;63(RR-1):1-14.

12. Petersen BW, Harms TJ, Reynolds MG, Harrison LH. Use of vaccinia virus

smallpox vaccine in laboratory and health care personnel at risk for occupational

exposure to orthopoxviruses - recommendations of the Advisory Committee on

Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep.

2016;65(10):257-262. DOI: 10.15585/mmwr.mm6510a2

13. Petersen BW, Damon IK, Pertowski CA, et al. Clinical guidance for smallpox

vaccine use in a postevent vaccination program. MMWR Recomm Rep.

2015;64(RR-2):1-26.

14. Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella:

recommendations of the Advisory Committee on Immunization Practices (ACIP).

MMWR Recomm Rep. 2007;56(RR-4):1-40.

15. Grossberg R, Harpaz R, Rubtcova E, Loparev V, Seward JF, Schmid DS.

Secondary transmission of varicella vaccine virus in a chronic care facility for

children. J Pediatr. 2006;148(6):842-844. DOI: 10.1016/j.jpeds.2006.01.038

16. Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants

and children: recommendations of the Advisory Committee on Immunization

Practices (ACIP). MMWR Recomm Rep. 2009;58(RR-2):1-25.

17. Anderson EJ. Rotavirus vaccines: viral shedding and risk of transmission. Lancet

Infect Dis. 2008;8(10):642-649. DOI: 10.1016/s1473-3099(08)70231-7

18. Sixbey JW. Routine immunizations and the immunosuppressed child. Adv

Pediatr Infect Dis. 1987;2:79-114.


19. Wright PF, Hatch MH, Kasselberg AG, Lowry SP, Wadlington WB, Karzon DT.

Vaccine-associated poliomyelitis in a child with sex-linked agammaglobulinemia.

J Pediatr. 1977;91(3):408-412. DOI: 10.1016/S0022-3476(77)81309-7

20. Wyatt HV. Poliomyelitis in hypogammaglobulinemics. J Infect Dis.

1973;128(6):802-806. DOI: 10.1093/infdis/128.6.802

21. Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive

poliomyelitis secondary to vaccination of an immunodeficient child. N Engl J

Med. 1977;297(5):241-245. DOI: 10.1056/nejm197708042970503

22. CDC. Disseminated Mycobacterium bovis infection from BCG vaccination of a

patient with acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly

Rep. 1985;34(16):227-228.

23. Ninane J, Grymonprez A, Burtonboy G, Francois A, Cornu G. Disseminated BCG

in HIV infection. Arch Dis Child. 1988;63(10):1268-1269. DOI:

10.1136/adc.63.10.1268

24. Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS.

Disseminated vaccinia in a military recruit with human immunodeficiency virus

(HIV) disease. N Engl J Med. 1987;316(11):673-676. DOI:

10.1056/nejm198703123161106

25. CDC. Measles pneumonitis following measles-mumps-rubella vaccination of a

patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep.

1996;45(28):603-606.

26. Cono J, Casey CG, Bell DM. Smallpox vaccination and adverse reactions.

Guidance for clinicians. MMWR Recomm Rep. 2003;52(RR-4):1-28.

27. Derryck A, LaRussa P, Steinberg S, Capasso M, Pitt J, Gershon AA. Varicella and

zoster in children with human immunodeficiency virus infection. Pediatr Infect

Dis J. 1998;17(10):931-933. DOI: 10.1097/00006454-199810000-00023

28. Levin MJ, Gershon AA, Weinberg A, Song LY, Fentin T, Nowak B. Administration

of live varicella vaccine to HIV-infected children with current or past significant

depression of CD4(+) T cells. J Infect Dis. 2006;194(2):247-255. DOI:

10.1086/505149


29. Sprauer MA, Markowitz LE, Nicholson JK, et al. Response of human

immunodeficiency virus-infected adults to measles-rubella vaccination. J Acquir

Immune Defic Syndr. 1993;6(9):1013-1016.

30. McLaughlin M, Thomas P, Onorato I, et al. Live virus vaccines in human

immunodeficiency virus-infected children: a retrospective survey. Pediatrics.

1988;82(2):229-233.

31. Onorato IM, Markowitz LE, Oxtoby MJ. Childhood immunization, vaccine-

preventable diseases and infection with human immunodeficiency virus. Pediatr

Infect Dis J. 1988;7(8):588-595.

32. Palumbo P, Hoyt L, Demasio K, Oleske J, Connor E. Population-based study of

measles and measles immunization in human immunodeficiency virus-infected

children. Pediatr Infect Dis J. 1992;11(12):1008-1014.

33. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles,

rubella, congenital rubella syndrome, and mumps, 2013: summary


MMWR Recomm Rep. 2013;62(RR-4):1-34.

34. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster:


MMWR Recomm Rep. 2008;57(RR-5):1-30; quiz CE32-34.

35. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious

complications among hematopoietic cell transplantation recipients: a global

perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. DOI:

10.1016/j.bbmt.2009.06.019

36. Ljungman P, Cordonnier C, Einsele H, et al. Vaccination of hematopoietic cell

transplant recipients. Bone Marrow Transplant. 2009;44(8):521-526. DOI:

10.1038/bmt.2009.263

37. American Academy of Pediatrics. Immunization in special clinical circumstances.

In: Pickering L, Baker C, Kimberlin D, Long S, eds. Red Book: 2009 Report of the

Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American

Academy of Pediatrics; 2009.


38. Staples JE, Bocchini JA, Jr., Rubin L, Fischer M. Yellow fever vaccine booster

doses: Recommendations of the Advisory Committee on Immunization Practices,

2015. MMWR Morb Mortal Wkly Rep. 2015;64(23):647-650.

39. CDC. Haemophilus b conjugate vaccines for prevention of Haemophilus

influenzae type b disease among infants and children two months of age and

older. Recommendations of the Immunization Practices Advisory Committee


40. CDC. Prevention of pneumococcal disease: recommendations of the Advisory

Committee on Immunization Practices (ACIP). MMWR Recomm Rep.

1997;46(RR-8):1-24.

41. Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and

children - use of 13-valent pneumococcal conjugate vaccine and 23-valent

pneumococcal polysaccharide vaccine - recommendations of the Advisory

Committee on Immunization Practices (ACIP). MMWR Recomm Rep.

2010;59(RR-11):1-18.

42. Brodtman DH, Rosenthal DW, Redner A, Lanzkowsky P, Bonagura VR.

Immunodeficiency in children with acute lymphoblastic leukemia after

completion of modern aggressive chemotherapeutic regimens. J Pediatr.

2005;146(5):654-661. DOI: 10.1016/j.jpeds.2004.12.043

43. American Academy of Pediatrics. Passive immunization. In: Pickering L, Baker C,

Kimberlin D, Long S, eds. Red Book: 2012 Report of the Committee on Infectious

Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

44. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of

the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm

Rep. 2010;59(RR-7):1-27.

8. altered immunocompetence8. altered immunocompetence . updates . ... they are temperature...

Documents